Since its discovery a century ago, the role of the renin angiotensin aldosterone system (RAAS) as an endocrine system involved in BP and fluid electrolyte regulation has been well established.1 Recent clinical trial evidence suggests that the RAAS may influence large vessel atherosclerosis and cardiovascular morbidity and mortality independently of Bp2. Atheromatous lesions result from an excessive inflammatory-fibroproliferative response to various forms of insult3. Through promotion of vasoconstriction, vascular smooth muscle cell growth, inflammation, generation of reactive oxygen species, thrombosis and vascular remodeling, angiotensin II has been identified as a key mediator in the process of atherogenesis.4 
Renin is of considerable importance as the first and rate limiting step in the RAAS system. It was noted as long ago as 1972 that hypertensive patients with high renin levels were more likely than those with normal or low renin levels to experience myocardial infarcts. Synthesis and secretion of renin by kidney juxtaglomerular cells is upregulated by cAMP, (mainly through beta 1 adrenergic receptor agonism), and down regulated by angiotensin II and intracellular calcium, in response to salt load, renal perfusion pressure, noradrenaline and renal prostaglandins.5 Several DNA elements in the distal and proximal promoter regions as well as in intron 1 have been implicated in cAMP regulation. A high molecular weight inactive renin is formed when renin combines with its endogenous inhibitor renin binding protein (ReBP).6 
Dispite renin being the key enzyme of the RAAS system, and therefore a good candidate quantitative trait locus for elucidating the molecular and genetic influences implicated in the molecular etiology of essential hypertension, a consensus concerning the nature, frequency and functionality of SNPs in the renin gene has not yet been reached.7 A very small sib-pair analysis (66 dizygotic twins and their parents) found both diastolic and systolic BP to be linked to the renin gene locus.8 However two other linkage studies yielded negative results.9,10 Studies in Japanese, Chinese, Dutch, Arab and American cohorts suggest that a BglI and/or an MboI dimorphisms (located respectively in the first and ninth introns of the renin gene) may be associated with essential hypertension, stroke and diabetic nephropathy.11-14 
More recently Fuchs and colleagues described two new polymorphisms in the enhancer region.15 They went on to show that one of these (−5312 C/T) appears to influence in vitro gene expression—the T allele variant was associated with a 40% increase in renin gene transcription. A further study of a large community dwelling population (n=390) has shown that T allele carriers of the (−5312 C/T) polymorphism have significantly increased office and ambulatory blood pressures (mean difference 2-3 mm Hg).16 
It is an object of the invention to provide a predictive assay for response to blood pressure lowering therapy.